United States - English - NLM (National Library of Medicine)
CLOTRIMAZOLE TOPICAL SOLUTION USP, 1% - clotrimazole topical solution usp,
Tasman Pharma Inc.
Clotrimazole Topical Solution USP, 1%
FOR EXTERNAL USE ONLY.
NOT FOR OPHTHALMIC USE.
This product is also available without a prescription.
Clotrimazole topical solution USP, 1% contains 10 mg clotrimazole USP, a synthetic antifungal agent
having the chemical name 1-(o-Chloro-α,α-diphenylbenzyl) imidazole with the following structural
MOLECULAR FORMULA C
MOLECULAR WEIGHT 344.85
Clotrimazole is an odorless, white crystalline substance. It is practically insoluble in water, sparingly
soluble in ether and very soluble in polyethylene glycol 400, ethanol, and chloroform.
Each mL of clotrimazole topical solution USP, 1% contains 10 mg clotrimazole USP in a nonaqueous
vehicle of polyethylene glycol 400.
Clotrimazole is a broad-spectrum antifungal agent that is used for the treatment of dermal infections
caused by various species of pathogenic dermatophytes, yeasts, and Malassezia furfur. The primary
action of clotrimazole is against dividing and growing organisms.
In vitro, clotrimazole exhibits fungistatic and fungicidal activity against isolates of Trichophyton rubrum,
Trichophyton mentagrophytes, Epidermophyton floccosum, Microsporum canis, and Candida species
including Candida albicans. In general, the in vitro activity of clotrimazole corresponds to that of
tolnaftate and griseofulvin against the mycelia of dermatophytes (Trichophyton, Microsporum, and
Epidermophyton), and to that of the polyenes (amphotericin B and nystatin) against budding fungi
(Candida). Using an in vivo (mouse) and an in vitro (mouse kidney homogenate) testing system,
clotrimazole and miconazole were equally effective in preventing the growth of the pseudomycelia and
mycelia of Candida albicans.
Strains of fungi having a natural resistance to clotrimazole are rare. Only a single isolate of Candida
guilliermondi has been reported to have primary resistance to clotrimazole.
No single-step or multiple-step resistance to clotrimazole has developed during successive passages
of Candida albicans and Trichophyton mentagrophytes. No appreciable change in sensitivity was detected
after successive passages of isolates of C. albicans, C. krusei, or C. pseudotropicalis in liquid or solid
media containing clotrimazole. Also, resistance could not be developed in chemically induced mutant
strains of polyene-resistant isolates of C. albicans.
Slight, reversible resistance was noted in three isolates of C. albicans tested by one investigator. There
is a single report that records the clinical emergence of a C. albicans strain with considerable resistance
to flucytosine and miconazole, and with cross-resistance to clotrimazole; the strain remained sensitive
to nystatin and amphotericin B.
In studies of the mechanism of action, the minimum fungicidal concentration of clotrimazole caused
leakage of intracellular phosphorus compounds into the ambient medium with concomitant breakdown of
cellular nucleic acids and accelerated potassium efflux. Both these events began rapidly and extensively
after addition of the drug.
Clotrimazole appears to be well absorbed in humans following oral administration and is eliminated
mainly as inactive metabolites. Following topical and vaginal administration, however, clotrimazole
appears to be minimally absorbed.
Six hours after the application of radioactive clotrimazole 1% cream and 1% solution onto intact and
acutely inflamed skin, the concentration of clotrimazole varied from 100 mcg/cm , in the stratum
corneum to 0.5 to 1 mcg/cm in the stratum reticulare, and 0.1 mcg/cm in the subcutis.
No measurable amount of radioactivity (≤0.001 mcg/mL) was found in the serum within 48 hours after
application under occlusive dressing of 0.5 mL of the solution or 0.8 g of the cream.
Only 0.5% or less of the applied radioactivity was excreted in the urine.
Following intravaginal administration of 100 mg
C-clotrimazole vaginal tablets to nine adult females,
an average peak serum level, corresponding to only 0.03 µg equivalents/mL of clotrimazole, was
reached 1 to 2 days after application. After intravaginal administration of 5 g of 1%
vaginal cream containing 50 mg active drug, to five subjects (one with candidal colpitis), serum levels
corresponding to approximately 0.01 µg equivalents/mL were reached between 8 and 24 hours after
INDICATIONS AND USAGE
Prescription clotrimazole topical solution product is indicated for the topical treatment of candidiasis
due to Candida albicans and tinea versicolor due to Malassezia furfur.
This formulation is also available as a nonprescription product which is indicated for the topical
treatment of the following dermal infections: tinea pedis, tinea cruris, and tinea corporis due to
Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton fluoccosum, and Microsporum canis.
Topical antifungal agents are contraindicated in those patients with a history of hypersensitivity to any
of the components of the preparation.
Clotrimazole topical solution is not for ophthalmic use.
If irritation or sensitivity develops with the use of clotrimazole, treatment should be discontinued and
appropriate therapy instituted.
Information for Patients
This information is intended to aid in the safe and effective use of this medication. It is not a disclosure
of all possible adverse or intended effects.
The patient should be advised to:
1. Use the medication for the full treatment time even though the symptoms may have improved. Notify
the physician if there is no improvement after 4 weeks of treatment.
2. Inform the physician if the area of application shows signs of increased irritation (redness, itching,
burning, blistering, swelling, oozing) indicative of possible sensitization.
3. Avoid sources of infection or reinfection.
If there is lack of response to clotrimazole, appropriate microbiological studies should be repeated to
confirm the diagnosis and rule out other pathogens before instituting another course of antimycotic
Synergism or antagonism between clotrimazole and nystatin, or amphotericin B, or flucytosine against
strains of C. albicans has not been reported.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
An 18-month oral dosing study with clotrimazole in rats has not revealed any carcinogenic effect.
In tests for mutagenesis, chromosomes of the spermatophores of Chinese hamsters which had been
exposed to clotrimazole were examined for structural changes during the metaphase.
Prior to testing, the hamsters had received five oral clotrimazole doses of 100 mg/kg body weight. The
results of this study showed that clotrimazole had no mutagenic effect.
Usage in Pregnancy
The disposition of
C-clotrimazole has been studied in humans and animals. Clotrimazole is very
poorly absorbed following dermal application or intravaginal administration to humans. (See
In clinical trials, use of vaginally applied clotrimazole in pregnant women in their second and third
trimesters has not been associated with ill effects.
There are, however, no adequate and well-controlled studies in pregnant women during the first
trimester of pregnancy.
Studies in pregnant rats with intravaginal doses up to 100 mg/kg have revealed no evidence of harm to
the fetus due to clotrimazole.
High oral doses of clotrimazole in rats and mice ranging from 50 to 120 mg/kg resulted in
embryotoxicity (possibly secondary to maternal toxicity), impairment of mating, decreased litter size and
number of viable young and decreased pup survival to weaning. However, clotrimazole was not
teratogenic in mice, rabbits and rats at oral doses up to 200, 180 and 100 mg/kg, respectively. Oral
absorption in the rat amounts to approximately 90% of the administered dose.
Because animal reproduction studies are not always predictive of human response, this drug should be
used only if clearly indicated during the first trimester of pregnancy.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human
milk, caution should be exercised when clotrimazole is used by a nursing woman.
Safety and effectiveness in pediatric patients have been established for clotrimazole when used as
indicated and in the recommended dosage.
The following adverse reactions have been reported in connection with the use of clotrimazole:
erythema, stinging, blistering, peeling, edema, pruritius, urticaria, burning, and general irritation of the
Acute overdosage with topical application of clotrimazole is unlikely and would not be expected to
lead to a life-threatening situation.
DOSAGE AND ADMINISTRATION
Gently massage sufficient clotrimazole topical solution USP, 1% into the affected and surrounding skin
areas twice a day, in the morning and evening.
Clinical improvement, with relief of pruritus, usually occurs within the first week of treatment with
clotrimazole topical solution USP, 1%. If the patient shows no clinical improvement after 4 weeks of
treatment with clotrimazole topical solution USP, 1%, the diagnosis should be reviewed.
Clotrimazole topical solution USP, 1% is supplied in 30 mL plastic bottles (NDC 72641-001-30);
boxes of one.
Store between 2° to 30°C (36° to 86°F).
Mfd. for: Tasman Pharma Inc.,
Warminster, PA 18974.
Made in New Zealand
Revised: February, 2019 308736
PRINCIPAL DISPLAY PANEL - 30 mL Bottle Carton
Keep this and all
medications out of the
reach of children.
Rx only 30 mL
Tasman Pharma Inc.
CLOTRIMAZOLE TOPICAL SOLUTION USP, 1%
clotrimazole topical solution usp, 1% solution
Product T ype
HUMAN PRESCRIPTION DRUG
Ite m Code (Source )
NDC:726 41-0 0 1
Route of Administration
Active Ingredient/Active Moiety
Basis of Strength
Stre ng th
Clo trima zo le (UNII: G0 7GZ9 7H6 5) (Clo trimazo le - UNII:G0 7GZ9 7H6 5)
Clo trima z o le
10 mg in 1 mL
Stre ng th
po lyethylene g lyco l 4 0 0 (UNII: B6 9 78 9 4SGQ)
Marketing Start Date
Marketing End Date
NDC:726 41-0 0 1-30
1 in 1 CARTON
0 7/25/20 19
30 mL in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct
Marke ting Cate gory
Application Numbe r or Monograph Citation
Marke ting Start Date
Marke ting End Date
0 7/25/20 19
T asman Pharma Inc. (080860172)